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1.
Front Surg ; 11: 1390038, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38712337

RESUMO

Introduction: Transumbilical laparoscopy (TUL) has emerged as a promising technique for establishing pneumoperitoneum in laparoscopic cholecystectomy, offering potential safety, feasibility, and clinical benefits. This retrospective multicentre study aims to evaluate the efficacy and outcomes of TUL in the management of gallbladder diseases. Methods: A retrospective analysis was conducted on a cohort of 2,543 patients who underwent TUL between 2011 and 2021 across various medical institutions in Italy. Data collection included demographic, clinical, intraoperative, and postoperative parameters. Standardized protocols were followed for preoperative and postoperative management. The TUL technique involved precise anatomical incision and trocar placement. Results: The study demonstrated favorable outcomes associated with TUL, including a low conversion rate to open surgery (0.55%), minimal intraoperative complications (0.16%), and short hospital stays (average 2.4 days). The incidence of incisional hernias was notably low (0.4%). Comparison with existing literature revealed consistent findings and provided unique insights into the advantages of TUL. Discussion: Despite limitations, such as the absence of a control group and the retrospective nature of the study, the findings contribute valuable insights to the literature. They inform surgical decision-making and advance patient care in laparoscopic cholecystectomy for gallbladder diseases. Conclusion: Transumbilical laparoscopy shows promise as a safe and feasible technique for establishing pneumoperitoneum in laparoscopic cholecystectomy. The study's findings support its clinical benefits, including low conversion rates, minimal complications, and short hospital stays. Further research, including prospective studies with control groups, is warranted to validate these results and optimize patient outcomes.

2.
Front Surg ; 11: 1370370, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38496209

RESUMO

Background: Colovesical fistulas (CVFs) pose a challenge in diverticulitis, affecting 4% to 20% of sigmoid colon cases. Complicated diverticular disease contributes significantly, accounting for 60%-70% of all CVFs. Existing studies on laparoscopic CVF management lack clarity on its effectiveness in diverticular cases compared to open surgery. This study redefines paradigms by assessing the potentiality, adequacy, and utility of laparoscopy in treating CVFs due to complicated diverticular disease, marking a paradigm shift in surgical approaches. Methods: Conducting a retrospective analysis at Ospedale Monaldi A.O.R.N dei Colli and University Federico II, Naples, Italy, patients undergoing surgery for CVF secondary to diverticular disease between 2010 and 2020 were examined. Comprehensive data, including demographics, clinical parameters, preoperative diagnoses, operative and postoperative details, and histopathological examination, were meticulously recorded. Patients were classified into open surgery (Group A) and laparoscopy (Group B). Statistical analysis used IBM SPSS Statistic 19.0. Results: From January 2010 to December 2020, 76 patients underwent surgery for colovesical fistula secondary to diverticular disease. Laparoscopic surgery (Group B, n = 40) and open surgery (Group A, n = 36) showed no statistically significant differences in operative time, bladder suture, or associated procedures. Laparoscopy demonstrated advantages, including lower intraoperative blood loss, reduced postoperative primary ileus, and a significantly shorter length of stay. Postoperative morbidity differed significantly between groups. Mortality occurred in Group A but was unrelated to surgical complications. No reoperations were observed. Two-year follow-up revealed no fistula recurrence. Conclusion: This pivotal study marks a paradigm shift by emphasizing laparoscopic resection and primary anastomosis as a safe and feasible option for managing CVF secondary to diverticular disease. Comparable conversion, morbidity, and mortality rates to the open approach underscore the transformative potential of these findings. The study's emphasis on patient selection and surgeon experience challenges existing paradigms, offering a progressive shift toward minimally invasive solutions.

3.
Cancer Drug Resist ; 6(3): 447-467, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842235

RESUMO

Early identification of breast cancer (BC) patients at a high risk of progression may aid in therapeutic and prognostic aims. This is especially true for metastatic disease, which is responsible for most cancer-related deaths. Growing evidence indicates that the translationally controlled tumor protein (TCTP) may be a clinically relevant marker for identifying poorly differentiated aggressive BC tumors. TCTP is an intriguing protein with pleiotropic functions, which is involved in multiple signaling pathways. TCTP may also be involved in stress response, cell growth and proliferation-related processes, underlying its potential role in the initiation of metastatic growth. Thus, TCTP marks specific cancer cell sub-populations with pronounced stress adaptation, stem-like and immune-evasive properties. Therefore, we have shown that in vivo phospho-TCTP levels correlate with the response of BC cells to anti-HER2 agents. In this review, we discuss the clinical relevance of TCTP for personalized therapy, specific TCTP-targeting strategies, and currently available therapeutic agents. We propose TCTP as an actionable clinically relevant target that could potentially improve patient outcomes.

4.
J Clin Med ; 12(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36675381

RESUMO

Temporary loop ileostomy is usually performed to protect distal anastomosis or to treat urgent surgical cases. The aim of this study is to evaluate whether, after primary urgent stoma construction, patients undergoing ileostomy reversal have different postoperative outcomes compared with patients who have protective stoma performed in an elective setting. A retrospective observational study was conducted including patients who underwent ileostomy reversal. Baseline patient characteristics and perioperative outcomes were collected in a single database. The overall morbidity rate during recovery was fixed as a primary outcome. Between 2011 and 2021, the complete data records of 145 patients were evaluated. After ileostomy reversal, the postoperative morbidity rate did not differ between groups (14.4% vs. 11.5%, p = 0.790). Even considering each complication, such as ileus, small bowel obstruction, bleeding and wound infection, no significant difference was detected. Similarly, the time to first flatus was 2.25 ± 1.24 vs. 2.1 ± 0.99 (p = 0.379) and the length of hospital stay was 5.43 ± 3.03 vs. 5.84 ± 5.15 (p = 0.568). The only significant factor associated with postoperative complications on logistic regression analysis was the presence of comorbidities (OR 4.49; 95% CI 1.19-29.4, p = 0.05). In the present cohort of patients, there was no difference in the postoperative complication rate after stoma closure following elective or urgent indication for surgery.

5.
Minerva Surg ; 78(2): 129-138, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35708447

RESUMO

BACKGROUND: In this study we described our experience in decreasing morbidity by performing a few changes during and after the Ivor Lewis esophagectomy. METHODS: This is a retrospective single center experience comparing a control period (group A) and a study period (group B) in patients who underwent esophagectomy for esophageal cancer (control group: 23; study group: 17). Control group had postero-lateral thoracotomy and a gastric tube without aspiration during postoperative period. Study group had limited lateral muscle sparing thoracotomy and postoperatively the gastric tube was routinely left for 1 week with intermittent aspiration (10 times every two hours for 1 week). RESULTS: Average operation time was 312±56 minutes in control period, in study period 189±36 min. Average ICU stay was 10 (7-32) days in the control group, in study group 4 (1-8) days. Anastomotic leak rate was significantly higher in control vs. study group (53.3% vs. 16.6%; P<0.05). Respiratory complications were significantly lower in the study group (47.8% vs. 17.6%). CONCLUSIONS: The combination of a limited lateral thoracotomy and postoperative intermittent aspiration seem to reduce the rate of respiratory and anastomotic complication after Ivor-Lewis' procedure.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Humanos , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Complicações Pós-Operatórias , Estudos Retrospectivos , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Morbidade
6.
Ann Med Surg (Lond) ; 78: 103668, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35734727

RESUMO

The existence of a close association between disease of the biliary tract and disease of the heart is known from the mists of time. Acute acalculous cholecystitis (AAC) can be defined as an acute necro inflammatory disease of the gallbladder in the absence of cholelithiasis. AAC is a challenging diagnosis. The atypical clinical onset associated to a paucity and similarity of symptoms and to laboratory data mimicking cardiovascular disease (CVD) often results in under and misdiagnosed cases. Moreover, AAC has commonly a fulminant course compared to calculous cholecystitis and it is often associated with gangrene, perforation and empyema as well as considerable morbidity and mortality (up 50%). Early diagnosis is crucial to a prompt treatment in order to avoid complications and to increase survivability. Even today, although scientific evidence dating two hundred years has shown a close association between AAC and CVD, due to the lack of RCT, there is still a lot of confusion regarding the relationship and consequently the clinical management AAC and CVD. In addition, emergency physicians are not always familiar with transient ECG changes with AAC. The aim of this review was to provide evidence regarding epidemiology, pathophysiology, clinical presentation and treatment of the complex association between AAC and CVD. Our main findings indicate that AAC should be suspected after each general disease leading to hypoperfusion such as cardiovascular diseases or cerebrovascular diseases or major heart or aortic surgery. ECG changes in absence of significant laboratory data for IMA (Acute myocardial infarction) could be related to a misdiagnosed AAC. US - Ultrasonography-plays a key role in the early diagnosis and also in the follow up of AAC. Cholecystostomy and cholecystectomy as unique or sequential represent the two prevailing treatment options for AAC.

8.
Rev Cardiovasc Med ; 23(2): 61, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35229552

RESUMO

BACKGROUND: Current studies focus primarily on skeletal injuries following cardiopulmonary resuscitation (CPR). Few studies report on intrathoracic injuries (ITI) and none, to our knowledge, focus exclusively on cardiovascular injuries related to cardiac massage. This study was based on autopsy findings and assessed the incidence of non-skeletal CPR related injuries related to chest compression. METHODS: This was a retrospective forensic autopsy cohort study conducted in a single institution after resuscitation. Pathologists recorded autopsy data using standardized protocol contained information from external and internal examination of the body. RESULTS: Thirty-eight autopsy reports (21 males and 17 females), post- CPR-failure were studied. Heart lesions were reported in 19 patients (group A). The average age was 65.7 years (69.05 group A and 66.5 group B). Median weight was 75.2 Kg and was significantly higher in group B (p = 0.01). Pericardial lesions were identified in 6 patients in group A and 2 in group B (p = 0.2 ns). No significant difference was observed among the two groups (Table 4) with the exception of the average number of rib fractures which was higher in group A (p = 0.04). Autopsy findings revealed heart injuries in 50% of patients with a high prevalence (52.6%) of left ventricle injuries. CONCLUSION: Cardiac lesions represent frequent and serious complications of unsuccessful CPR. Correct performance of chest compressions according to guidelines is the best way to avoid these complications.


Assuntos
Reanimação Cardiopulmonar , Traumatismos Cardíacos , Fraturas das Costelas , Idoso , Reanimação Cardiopulmonar/efeitos adversos , Estudos de Coortes , Feminino , Traumatismos Cardíacos/diagnóstico , Traumatismos Cardíacos/epidemiologia , Traumatismos Cardíacos/etiologia , Humanos , Masculino , Estudos Retrospectivos , Fraturas das Costelas/diagnóstico , Fraturas das Costelas/epidemiologia , Fraturas das Costelas/etiologia
9.
Biomark Med ; 15(4): 307-318, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33590769

RESUMO

Cardiovascular disease includes health problems related to the heart, arteries and veins and is a significant healthcare problem worldwide. Cardiovascular disease may be acute or chronic and relapses are frequent. Biomarkers involved in this field may help clinicians and surgeons in diagnosis and adequate decision making. Relevant articles searched in the following databases Medline, Scopus, ScienceDirect, were retrieved and analysed. Several biomarkers have been identified and we analyzed those of most importance from a clinical and surgical point of view. Biomarkers can better identify high-risk individuals, facilitate follow-up process, provide information regarding prognosis and better tailor the most appropriate surgical treatment.


Assuntos
Biomarcadores/metabolismo , Doenças Cardiovasculares/cirurgia , Seleção de Pacientes , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Humanos , Prognóstico , Fatores de Risco
10.
Transl Oncol ; 14(3): 101013, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33516089

RESUMO

Copy Number Alterations (CNAs) represent the most common genetic alterations identified in ovarian cancer cells, being responsible for the extensive genomic instability observed in this cancer. Here we report the identification of CNAs in a cohort of Italian patients affected by ovarian cancer performed by SNP-based array. Our analysis allowed the identification of 201 significantly altered chromosomal bands (70 copy number gains; 131 copy number losses). The 3300 genes subjected to CNA identified here were compared to those present in the TCGA dataset. The analysis allowed the identification of 11 genes with increased CN and mRNA expression (PDCD10, EBAG9, NUDCD1, ENY2, CSNK2A1, TBC1D20, ZCCHC3, STARD3, C19orf12, POP4, UQCRFS1). PDCD10 was selected for further studies because of the highest frequency of CNA. PDCD10 was found, by immunostaining of three different Tissue Micro Arrays, to be over-expressed in the majority of ovarian primary cancer samples and in metastatic lesions. Moreover, significant correlations were found in specific subsets of patients, between increased PDCD10 expression and grade (p < 0.005), nodal involvement (p < 0.05) or advanced FIGO stage (p < 0.01). Finally, manipulation of PDCD10 expression by shRNA in ovarian cancer cells (OVCAR-5 and OVCA429) demonstrated a positive role for PDCD10 in the control of cell growth and motility in vitro and tumorigenicity in vivo. In conclusion, this study allowed the identification of novel genes subjected to copy number alterations in ovarian cancer. In particular, the results reported here point to a prominent role of PDCD10 as a bona fide oncogene.

11.
Updates Surg ; 72(2): 445-451, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32232743

RESUMO

Laparoscopy has gained wide acceptance due its benefits for patients. However, advanced laparoscopic procedures are still challenging. One critical issue is lack of stereoscopic vision. Despite its diffusion, the totally laparoscopic approach for right hemicolectomy (TLRC) is still debated due to its difficulty, particularly for fashioning of the ileocolic anastomosis. The aim of this multicenter study is to investigate whether 3D vision offers any advantages on surgical performance over 2D vision during TLRC. All data of consecutive patients who underwent elective TLRC for cancer at three Italian surgical centers with either 2D or 3D technology from January 2013 to December 2018 were retrieved from a computer-maintained database. A case-matched analysis using the Mantel-Haenszel method was performed. After matching, a total of 106 patients were analyzed with 53 patients in each group. Mean operative time was significantly longer for 2D-TLRC than for 3D-TLRC (153.2 ± 52.4 vs. 131 ± 51 min, p = 0.029) and a statistically significant difference in anastomosing time (p = 0.032, 19.2 ± 5.9 min vs. 21.7 ± 6.2 min for 3D and 2D group, respectively) was also recorded. No difference in the median number of harvested nodes (23 ± 11 vs. 21 ± 7 for 3D and 2D group, respectively; p = 0.48) was found. Neither intraoperative complications nor conversions occurred in the two groups. In conclusion, 3D vision appears to improve the performance of a TLRC by reducing operative time and making intracorporeal anastomosis easier. Prospective randomized studies are required to determine the real beneficial effects.


Assuntos
Colectomia/métodos , Imageamento Tridimensional/métodos , Laparoscopia/métodos , Cirurgia Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/métodos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento
12.
Minerva Chir ; 75(2): 77-82, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29963791

RESUMO

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) represents the most performed bariatric surgical procedure worldwide. Morbid Overweight in elderly patients is becoming a significant health problem even in Italy. As well as in younger age groups, bariatric surgery could be indicated even in this subset of patients. However the advantages and results of LSG in patients over 60 years old have received minimal attention. METHODS: The records of 375 patients underwent LSG between 2008 and 2016 were reviewed. In the entire series 18 patients were aged 60 years or older at the time of surgery. Since a 3 years follow-up was available for 12 patients out of the 18 aged over 60 we included in the study only these. General epidemiologic data, clinical findings, BMI and comorbidities surgical treatment and follow-up data were collected; postoperative measurements such as operative time, intraoperative complications, mortality rate, length of stay, incidence of early and late complications, Body mass Index (BMI), excess weight loss rate (EWL%) and comorbidities resolution were also recorded. RESULTS: LSG was successfully performed for all geriatric patients. Global complications rate was 16.6% At 3 years mean BMI was 34.4±3.8 with a mean EWL% 66.1±31.9. Postoperative resolution of obesity comorbidities was observed; Hypertension (71.4%), type 2 Diabetes Mellitus (T2DM) (50.0%), obstructive sleep apnea syndrome (OSAS) (66.6%) respectively. No intraoperative complications or mortality were recorded. CONCLUSIONS: LSG offered cure in geriatric patients affected by morbid obesity for weight loss and comorbidities resolution. Larger studies are necessary to analyze and minimize the incidence of postoperative complications associated to this surgical procedure in elderly patients.


Assuntos
Cirurgia Bariátrica/métodos , Gastrectomia/métodos , Laparoscopia , Obesidade Mórbida/cirurgia , Fatores Etários , Idoso , Feminino , Seguimentos , Humanos , Complicações Intraoperatórias/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
13.
Am J Transl Res ; 11(3): 1771-1779, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30972200

RESUMO

Intraoperative auto-transfusion with the use of cell saver systems is routinely used to reduce the rate of packed red blood transfusion in major surgery. Nevertheless some concerns have been raised on possible risks of coagulation disorders. The aim of the study was to analyze the blood processed by the cell saver, ready to be re-infused to the patient, in order to individuate unexpected cellular components, that can favor coagulopathy. We tested the blood processed by the cell saver in thirteen patients undergoing coronary bypass surgery with Cellsearch®, ScreenCell®, Cytology and Immunofluorescence. Those four methods allowed us to look for the presence of unexpected cells, quantify and characterize them. Furthermore, the blood processed by the cell saver was mixed with the patient's peripheral blood and analyzed with the ROTEM® thromboelastography. The Cellsearch® revealed and counted a mean number of 1241 unexpected cells/7.5 ml in the blood processed by the cell saver. The ScreenCell® and Cytology confirmed the presence of non-hematological cells. Immunofluorescence showed positivity for Calretinin and WT-1, confirming the mesothelial origin. Moreover we detected a peculiar arrangement of the platelets around the mesothelial cells in a "cloud" form, suggesting platelet activation. The ROTEM® analysis showed a significantly longer clot formation time, smaller clot amplitude and maximum clot firmness, compared to controls. In conclusion we demonstrated the presence of mesothelial cells in the cell saving blood, ready to be auto-transfused. This finding can contribute to develop a platelet depletion coagulopathy, with coagulation factors consumption.

14.
Oncotarget ; 9(32): 22749-22768, 2018 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-29854313

RESUMO

In this study, we have set-up a routine pipeline to evaluate the clinical application of Oncomine™ Focus Assay, a panel that allows the simultaneous detection of single nucleotide hotspot mutations in 35 genes, copy number alterations (CNAs) in 19 genes and gene fusions involving 23 genes in cancer samples. For this study we retrospectively selected 106 patients that were submitted to surgical resection for lung, gastric, colon or rectal cancer. We found that 56 patients out of 106 showed at least one alteration (53%), with 47 patients carrying at least one relevant nucleotide variant, 10 patients carrying at least one CNA and 3 patients carrying one gene fusion. On the basis of the mutational profiles obtained, we have identified 22 patients (20.7%) that were potentially eligible for targeted therapy. The most frequently mutated genes across all tumor types included KRAS (30 patients), PIK3CA (16 patients), BRAF (6 patients), EGFR (5 patients), NRAS (4 patients) and ERBB2 (3 patients) whereas CCND1, ERBB2, EGFR and MYC were the genes most frequently subjected to copy number gain. Finally, gene fusions were identified only in lung cancer patients and involved MET [MET(13)-MET(15) fusion] and FGFR3 [FGFR3(chr 17)-TACC3(chr 11)]. In conclusion, we demonstrate that the analysis with a multi-biomarker panel of cancer patients after surgery, may present several potential advantages in clinical daily practice, including the simultaneous detection of different potentially druggable alterations, reasonable costs, short time of testing and automated interpretation of results.

16.
Int Wound J ; 15(5): 829-833, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29808553

RESUMO

Varicose veins (VVs) and varicose ulceration (VU) are usually considered non-life-threatening conditions, but in some cases they can lead to major complications such as fatal bleeding. The aim of this systematic review is to evidence the most updated information on bleeding from VV and VU. As evidence acquisition, we planned to include all the studies dealing with "Haemorrhage/Bleeding" and "VVs/VU". We excluded all the studies, which did not properly fit our research question, and with insufficient data. As evidence synthesis, of the 172 records found, after removing of duplicates, and after records excluded in title and abstract, 85 matched our inclusion criteria. After reading the full-text articles, we decided to exclude 68 articles because of the following reasons: (1) not responding properly to our research questions; (2) insufficient data; the final set included 17 articles. From literature searching, we identify the following main issues to be discussed in the review: epidemiology and predisposing factors, pathophysiology and forensic aspects, first aid. It has been estimated that deaths for bleeding due to peripheral venous problems account up to 0.01% of autopsy cases. From a pathological point of view, venous bleeding may arise from either acute or chronic perforation of an enlarged vein segment through the weakened skin. From a forensic point of view, in cases of fatal haemorrhage the death scene can even simulate non-natural events, due to crime or suicide. In most cases, incorrect first aid led to fatal complications. Further investigation on epidemiology and prevention measures are needed.


Assuntos
Causas de Morte , Hemorragia/etiologia , Hemorragia/mortalidade , Úlcera Varicosa/complicações , Varizes/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Oncotarget ; 9(35): 23960-23974, 2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29844865

RESUMO

The objective of this study was to investigate the mutational profiles of cancers arising in different colon segments. To this aim, we have analyzed 37 colon cancer samples by use of the Ion AmpliSeq™ Comprehensive Cancer Panel. Overall, we have found 307 mutated genes, most of which already implicated in the development of colon cancer. Among these, 15 genes were mutated in tumors originating in all six colon segments and were defined "common genes" (i.e. APC, PIK3CA, TP53) whereas 13 genes were preferentially mutated in tumors originating only in specific colon segments and were defined "site-associated genes" (i.e. BLNK, PTPRD). In addition, the presence of mutations in 10 of the 307 identified mutated genes (NBN, SMUG1, ERBB2, PTPRT, EPHB1, ALK, PTPRD, AURKB, KDR and GPR124) were found to be of clinical relevance. Among clinically relevant genes, NBN and SMUG1 were identified as independent prognostic factors that predicted poor survival in colon cancer patients. In conclusion, the findings reported here indicate that tumors arising in different colon segments present differences in the type and/or frequency of genetic variants, with two of them being independent prognostic factors that predict poor survival in colon cancer patients.

18.
Oncotarget ; 9(29): 20409-20425, 2018 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-29755661

RESUMO

The objective of this study was to determine the feasibility to detect copy number alterations in colon cancer samples using Next Generation Sequencing data and to elucidate the association between copy number alterations in specific genes and the development of cancer in different colon segments. We report the successful detection of somatic changes in gene copy number in 37 colon cancer patients by analysis of sequencing data through Amplicon CNA Algorithm. Overall, we have found a total of 748 significant copy number alterations in 230 significant genes, of which 143 showed CN losses and 87 showed CN gains. Validation of results was performed on 20 representative genes by quantitative qPCR and/or immunostaining. By this analysis, we have identified 4 genes that were subjected to copy number alterations in tumors arising in all colon segments (defined "common genes") and the presence of copy number alterations in 14 genes that were significantly associated to one specific site (defined "site-associated genes"). Finally, copy number alterations in ASXL1, TSC1 and IL7R turned out to be clinically relevant since the loss of TSC1 and IL7R was associated with advanced stages and/or reduced survival whereas copy number gain of ASXL1 was associated with good prognosis.

19.
J Exp Clin Cancer Res ; 37(1): 84, 2018 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-29665843

RESUMO

BACKGROUND: Improvement in genetic characterization of Colon Cancer (CC) patients is required to propose new potential targets, since surgical resection coupled to chemotherapy, presents several limits such as cancer recurrence and drug resistance. Targeted therapies have more efficacy and less toxicity than standard treatments. One of the most relevant cancer-specific actionable targets are receptor tyrosine kinases (RTKs) whose role in CC need to be better investigated. METHODS: We have analysed 37 CC patients using the Ion AmpliSeq™ Comprehensive Cancer Panel (CCP). We have confirmed the somatic nature of RET variants through Sanger sequencing and assessed RET activation status and protein expression by immunofluorescence and western-blot analyses. We have used RET mutant expression vectors to evaluate the effect of selected mutations in HEK293 cells by performing proliferation, migration and clonogenic assays. RESULTS: Among the 409 cancer-related genes included in the CCP we have focused on the RTKs. Overall, we have observed 101 different potentially damaging variants distributed across 31 RTK genes in 28 patients. The most frequently mutated RTKs were FLT4, ROS1, EPH7, ERBB2, EGFR, RET, FGFR3 and FGFR4. In particular, we have identified 4 different somatic variants in 10% of CC patients in RET proto-oncogene. Among them, we have demonstrated that the G533C variant was able to activate RET by promoting dimer formation and enhancing Y1062 phosphorylation. Moreover, we have demonstrated that RET G533C variant was able to stimulate anchorage-dependent proliferation, migration and clonogenic cell survival. Notably, the effects induced by the RET G533C variant were abolished by vandetanib. CONCLUSIONS: The discovery of pathogenic variants across RTK genes in 75% of the CC patients under analysis, suggests a previously underestimated role for RTKs in CC development. The identification of a gain-of-function RET mutation in CC highlights the potential use of RET in targeted therapy.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Idoso , Idoso de 80 Anos ou mais , Mutação com Ganho de Função , Humanos , Pessoa de Meia-Idade , Proto-Oncogene Mas , Transfecção
20.
Int J Surg ; 53: 53-58, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29555524

RESUMO

BACKGROUND: Choledocholithiasis occurs in 10-15% of patients with cholecystolithiasis. Despite the existence of many therapeutic options for the treatment of cholecystocholedocholithiasis, a sequential treatment in which pre-operative ERCP is combined with intraoperative cholangiography (IOC) and laparoscopic cholecystectomy (LC), is the most commonly accepted strategy. However, use of IOC in the "splitting treatment" of cholecystocholedocholithiasis is controversial. The aim of the present study is to investigate the utility of IOC in detecting residual stones in patients undergoing LC in the sequential treatment of common biliary duct or gallbladder stones. METHODS: Patients were recruited retrospectively among those who underwent IOC during LC, performed as second stage in the sequential treatment for cholecystocholedocholithiasis between 2010 and 2016. Demographic and clinical data were obtained from CPT codes at Ospedale Monaldi A.O.R.N dei Colli Naples, Italy. Data obtained from all pre-operative ERCP analyses were recorded, including cholangiogram findings and performance of sphincterotomy. Statistical analysis was carried out using the IBM SPSS Statistic 19.0 software package. RESULTS: Between January 2010 and December 2016 575 patients (343 males, 242 females) underwent IOC during LC for symptomatic cholecystitis due to cholelithiasis. Among patients accrued for the study, 143 underwent preoperative ERCP for suspicion of common biliary duct stones. At the time of pre-operative ERCP, 123 were found to have common biliary duct stones while 20 (15%) presented negative ERCP. Complete removal of stones was accomplished in 119 patients. Among these patients, 13 had residual common biliary duct stones diagnosed by IOC (11%). Two patients underwent laparoscopic bile duct revision and, last, two patients were referred for ERCP at a later point. It is of note that all patients who presented residual stones by IOC had undergone pre-operative sphincterotomy. CONCLUSION: This study demonstrates that IOC is particularly effective in detecting residual stones in patients undergoing LC in sequential treatment of common biliary duct and/or gallbladder stones, and may be used on a routine basis in the sequential treatment of cholecystocholedocholithiasis.


Assuntos
Colangiografia/métodos , Colecistectomia Laparoscópica/métodos , Colecistolitíase/cirurgia , Coledocolitíase/cirurgia , Cuidados Intraoperatórios/métodos , Adulto , Idoso , Ductos Biliares/cirurgia , Colangiopancreatografia Retrógrada Endoscópica , Colecistolitíase/complicações , Coledocolitíase/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
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